Abstract
BackgroundRetinitis pigmentosa is a heterogeneous group of inherited neurodegenerative retinal disorders characterized by a progressive peripheral vision loss and night vision difficulties, subsequently leading to central vision impairment. Chronic microglia activation is associated with various neurodegenerative diseases including retinitis pigmentosa. The objective of this study was to quantify microglia activation in the retina of P23H rats, an animal model of retinitis pigmentosa, and to evaluate the therapeutic effects of TUDCA (tauroursodeoxycholic acid), which has been described as a neuroprotective compound.MethodsFor this study, homozygous P23H line 3 and Sprague-Dawley (SD) rats were injected weekly with TUDCA (500 mg/kg, ip) or vehicle (saline) from 20 days to 4 months old. Vertical retinal sections and whole-mount retinas were immunostained for specific markers of microglial cells (anti-CD11b, anti-Iba1 and anti-MHC-II). Microglial cell morphology was analyzed and the number of retinal microglial was quantified.ResultsMicroglial cells in the SD rat retinas were arranged in regular mosaics homogenously distributed within the plexiform and ganglion cell layers. In the P23H rat retina, microglial cells increased in number in all layers compared with control SD rat retinas, preserving the regular mosaic distribution. In addition, a large number of amoeboid CD11b-positive cells were observed in the P23H rat retina, even in the subretinal space. Retinas of TUDCA-treated P23H animals exhibited lower microglial cell number in all layers and absence of microglial cells in the subretinal space.ConclusionsThese results report novel TUDCA anti-inflammatory actions, with potential therapeutic implications for neurodegenerative diseases, including retinitis pigmentosa.
Highlights
Retinitis pigmentosa is a heterogeneous group of inherited neurodegenerative retinal disorders characterized by a progressive peripheral vision loss and night vision difficulties, subsequently leading to central vision impairment
We address the hypothesis that the neuroprotective compound, tauroursodeoxycholic acid (TUDCA), is able to prevent microglial activation, modify its expression pattern and delay the photoreceptor cells loss in an animal model of Retinitis pigmentosa (RP)
Numerous amoeboid CD11b-positive cells were observed in all retinal layers, with greater presence in inner plexiform layer (IPL), outer plexiform layer (OPL) and the space that lies between the photoreceptors and the retinal pigment epithelium (RPE), the subretinal space (SS)
Summary
Retinitis pigmentosa is a heterogeneous group of inherited neurodegenerative retinal disorders characterized by a progressive peripheral vision loss and night vision difficulties, subsequently leading to central vision impairment. Retinitis pigmentosa (RP) is a type of hereditary retinal degeneration with high levels of clinical and genetic heterogeneity This neurodegenerative retinal disorder is characterized by a primary degeneration of the photoreceptor rods causing peripheral vision loss and night blindness. In response to negative stimulus, tissue injury or free radicals, microglial cells assume a reactive state, characterized by a shortening and widening of microglial processes [9]. These reactive microglial cells can progress into phagocytic microglial cells. Activated microglial cells have been observed in mouse models of autosomal recessive RP [10,11], in rds mice [12] and in rat models of inherited retinal degeneration, including Royal College of Surgeons rats [13]
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